The present invention relates generally to techniques for determining mass values from time-of-flight information in time-of-flight mass spectrometry, and more specifically to techniques for calibrating time-of-flight mass spectra to thereby improve the accuracy of such mass value determinations.
In the field of time-of-flight (TOF) mass spectrometry, instrumentation and operational techniques directed at maximizing mass resolution are known. An example of one such technique is detailed in U.S. Pat. Nos. 5,504,326, 5,510,613 and 5,712,479 to Reilly et al., each of which are assigned to the assignee of the present invention. The Reilly et al. references describe a spatial-velocity correlation focusing technique that provides for improved resolution in time-of-flight measurements. However, as with any TOF instrument, the measured time-of-flight data must be subsequently converted to corresponding mass values in order to provide useful mass information.
Accurate conversion of time-of-flight data to mass values typically requires calibration of experimentally measured time-of-flight mass spectra using known mass value information. Heretofore, various curve fitting techniques have been used for calibrating time of flight mass spectra. It is known that the mass-to-charge ratio (m/z) of an ion traveling through a TOF mass spectrometer is approximately proportional to the square of its time of flight, and this relationship is commonly used in known curve fitting techniques to numerically solve for a set of coefficients in a polynomial representation relating time-of-flight to mass. The exact equation used may vary depending upon the instrument configuration and accuracy required, and a variety of graphing, numerical and mass spectral analysis software packages are commercially available for rapidly performing such calibrations.
While curve fitting techniques have been widely accepted and used for performing mass spectra calibrations, such techniques have several drawbacks associated therewith. For example, all known curve fitting and neural network techniques are devoid of information contained in electrostatic ion calculations and are therefore independent of TOF mass spectrometer operating parameters. Ion times of flight, particularly when using delayed extraction techniques, have an infinite expansion of high order non-linearities that can adversely affect the accuracy of curve fitting techniques. Curve fitting techniques can compensate for such non-linearities by including additional terms in the series expansion of the mass/TOF equation, although a regression fit of mass calibrants to a function is generally devoid of information relating to instrument operating conditions that can describe ion behavior, and is therefore missing information that may be useful in mass calibration. A second drawback with known curve fitting techniques used for mass spectra calibration is that the accuracy of such techniques can decrease significantly outside of the mass range of the calibration.
What is therefore needed is an improved time-of-flight mass spectra calibration technique that addresses at least the foregoing drawbacks of known mass calibration techniques.
The foregoing shortcomings of the prior art are addressed by the present invention. In accordance with one aspect of the present invention, a system for calibrating time-of-flight (TOF) mass spectra comprises a memory having a plurality of TOF mass spectrometer instrument operational parameters and at least one known mass value and associated measured time of flight value stored therein, and a computer in communication with the memory. The computer is operable to compute a time of flight of said at least one known mass value as an electrostatic function of the plurality of instrument operational parameters and adjust at least one of the plurality of instrument operational parameters to thereby minimize a difference between the computed time of flight and the measured time of flight value.
In accordance with another aspect of the present invention, a method of calibrating time-of-flight (TOF) mass spectra comprises the steps of providing a plurality of TOF mass spectrometer instrument operational parameters, providing at least one known mass value and associated measured time of flight value therefore, computing a time of flight of said at least one known mass value as an electrostatic function of the plurality of instrument operational parameters, and adjusting at least one of the instrument operational parameters to thereby minimize a difference between the computed time of flight and the measured time of flight value.
In accordance with a further aspect of the present invention, a method of calibrating time-of-flight (TOF) mass spectra comprises the steps of providing a plurality of TOF mass spectrometer instrument operational parameters, providing at least one known mass value and associated measured time of flight value therefore, computing a time of flight of said at least one known mass value as an electrostatic function of the plurality of instrument operational parameters, and iteratively optimizing at least one of the plurality of instrument operating parameters until the time of flight computed as an electrostatic function of the plurality of instrument operating parameters matches the measured time of flight value within a predetermined error tolerance value.
One object of the present invention is to provide a system and method for improving the accuracy of mass value determinations based on time-of-flight information provided by a time-of-flight mass spectrometer.
Another object of the present invention is to improve the accuracy of mass value determinations by providing for an improved technique for calibrating time of flight mass spectra.
Yet another object of the present invention is to provide a time of flight mass spectra calibration technique that is based on physical operational parameters of the mass spectrometer instrument rather than on a conventional calibration equation containing a collection of terms representing approximate or arbitrary factors.
These and other objects of the present invention will become more apparent from the following description of the preferred embodiments.